SARS‐CoV‐2 omicron variant may present with severe sickle cell painful crisis: A report of two cases

Coronavirus disease 2019 (COVID‐19) is a respiratory viral illness that is caused by coronavirus 2 (SARS‐CoV‐2). The disease often presents with non‐specific symptoms such as fever, headache, and fatigue, accompanied by respiratory symptoms (e.g., cough and dyspnea) and other systemic involvement. Currently, the virus had shown significant changes and mutations that resulted in the emergence of different strains. Each strain varies in its virulence, disease severity, and the response of the body''s immune system. Sickle cell disease characterized by hemolytic anemia particularly in associated with stress. Patients with sickle cell disease infected with SARS‐CoV‐2 are reported to have increased risk for hospitalization, thrombosis, and other complications compared with non‐sickle cell patients. The Omicron variant causes mild disease in general population; however, in patients with sickle cell disease, the data are limited. We present two patients known to have sickle cell disease presented with a severe acute painful crisis that required hospitalization after infection with Omicron variant of the SARS‐CoV‐2 virus.     

17 alpha‐hydroxylase deficiency: A case report of young Chinese woman with a rare gene mutation

We report a young adult woman with 17 alpha‐hydroxylase deficiency (17α‐OHD) in Shandong province of China. The patient carried compound heterozygous mutations in the CYP17A1 gene: c.985–987 delinsAA (p.Tyr329LysfsX90) and c.1486C > T (p.Arg496Cys). The patient''s hypertension and hypokalemia were resolved after taking medications of glucocorticoid, aldactone, and calcium antagonists.     

Prenatal diagnosis of thalassemia in 695 pedigrees from southeastern China: a 10‐year follow‐up study

Thalassaemia is highly prevalent in southeastern China. This 10‐year follow‐up study aimed to characterize the genotype and karyotype of thalassaemia in fetal samples derived from thalassemia carriers in Fujian province, southeastern China. A total of 476 prenatal samples from 472 couples carrying α‐thalassaemia traits and 224 samples from 223 couples carrying β‐thalassaemia traits were collected for STR analysis, detection of thalassemia genotypes and karyotyping. The common deletional α‐thalassemias and rare thalassemia genotypes were detected using Gap‐PCR assay, and the common β‐globin gene mutations were detected using PCR‐RDB assay. We detected 43.49% prevalence of α‐thalassaemia minor, 26.05% prevalence of α‐thalassaemia intermediate and major and 1.89% prevalence of rare form among the 476 prenatal samples from couples with α‐thalassaemia, and 85 fetuses with β‐thalassemia heterozygote, 16 with homozygote and 21 with double heterozygote, and a rare β^{IVS−2−654(C→T)}/Chinese G_γ (^Aγδβ)⁰ genotype among the 224 prenatal samples from couples with β‐thalassemia. Karyotyping showed 7 fetuses with abnormal karyotypes. Totally 153 pregnancies were terminated, and genetic diagnosis of thalassemia using fetal umbilical cord blood following induction of labor showed consistent results with prenatal diagnosis. No thalassemia phenotypes were identified in normal infants half a year after birth, and the infants with α‐thalassemia and β‐thalassemia minor had no or mild anemia symptoms, but normal development, while 15 babies with hemoglobin H disease presented moderate anemia symptoms. Our data suggest the pregestational screening of thalassemia, notably compound and rare forms of thalassemia, for couples carrying thalassemia traits.     

Impact of IFN‐β1a in treatment of a COVID‐19 patient with beta thalassemia and diabetes mellitus: A case report

Patients with chronic diseases are severely affected by acute coronavirus syndrome. In this regard, patients with beta thalassemia intermedia and diabetes mellitus (DM) are also at high risk for coronavirus‐induced respiratory failure. The present study aimed to report a case with COVID‐19 with a history of chronic diseases, beta thalassemia intermedia, and DM. A 25‐year‐old man visited with complaints of severe shortness of breath, fever, cough without sputum, and tachypnea and admitted to the Intensive Care Unit. The patient had a history of DM, beta thalassemia intermedia, and pervious history of the splenectomy. In peripheral complete blood count (CBC diff), the number of white blood cell count was 41,100 of which 38.6% were lymphocytes. We measured the normal platelet count, hemoglobin level (9.4), and red blood cell count (3.56). ESR was 97, CRP = pos+++ and PCR was positive. The high‐resolution lung CT indicated ground glass opacities in peripheral areas. The patient underwent 13 days of oxygen therapy with reservoir bag‐mask, non‐invasive ventilation, nasal oxygen, and pharmacological treatment with IFN‐β1a and meropenem, and finally discharged with an improvement of the clinical condition. Timely initiation of treatment is very important and significant for patients with beta thalassemia intermedia with COVID‐19, especially despite the underlying disease of DM. According to the present report, the use of IFN‐β1a was effective as a treatment option for COVID‐19.     

DNA testing for sickle cell anemia in Africa: Implementation choices for the Democratic Republic of Congo

BackgroundHemoglobin‐based tests form the reference diagnostic test for SCA. In limited resource countries, these tests face limitations including cost, low sensitivity due to recurrent transfusions in endemic malaria region, and interference from fetal hemoglobin in neonatal diagnostic. This study aimed at adapting DNA‐based SCA tests to limited resource countries and evaluating the economic benefit.Methods338 participants were recruited in the Democratic Republic of Congo, sorted in 3 cohorts based on venous blood, umbilical cord blood (UCB) and buccal swab sampling. RFLP was performed to identify mutated allele. The feasibility and technical validity of this RFLP was evaluated for specimens collected on DBS cards and on EDTA tubes. RFLP on DBS stored at room temperature was regularly repeated to assess sample conservation. Finally, the cost analysis was performed.ResultsDBS cards yielded identical results to extracted DNA. Repeated testing returned the same result after four years. The DBS‐based test performed on UCB or on buccal swab had a sensitivity and a precision of 100%. Cost comparison indicated that our approach costs half price of the widely used isoelectrofocussing of hemoglobin.ConclusionThe implemented DNA‐based test approach overcomes the limitations faced by hemoglobin‐based tests, while being more affordable. We propose to implement the RFLP test as a first line diagnostic test after transfusion and as second tiers for newborn screening. However, users should be aware that this test is unable to differentiate HbC from HbS or identify other point mutation of gene deletion of HBB gene.     

Novel homozygous nonsense mutation in the P5′N‐1 coding gene as an alternative cause for hereditary anemia with basophilic stippling

Hereditary pyrimidine 5‐nucleotidase (P5′N‐1) deficiency is a very rare disorder. Here, we describe a new mutation in a Turkish family. Although functional tests have not been performed, our findings confirm that the homozygous mutational state leads to clinical manifest P5′N‐1 deficiency, while heterozygosity does not lead to hemolysis or anemia.     

Doppler ultrasonographic evaluation of celiac and mesenteric arteries in subjects with sickle cell disease

Vasculopathy, as occurring in sickle cell disease (SCD), can affect celiac and mesenteric arteries and result in stenosis, with elevated peak systolic velocity (PSV) on Doppler ultrasonography. In six subjects with confirmed SCD in steady state, routine Doppler ultrasonographic examination discovered features of celiac artery (CA) or superior mesenteric artery (SMA) stenosis with CA PSV >200 cm/s (median = 222.8 cm/s; range = 201.5-427.1 cm/s) and/or SMA PSV >275 cm/s (median 183.2 cm/s; range = 87.8-289.3 cm/s). Among the six subjects, five had elevated soluble P-selectin values (median 72.55 ng/mL), while all six (100%) had elevated cystatin C levels (median 4.15 mg/L). Peripheral oxygen saturation was suboptimal in five subjects. All subjects had low hemoglobin concentration levels (median 8.5 g/dL) while four had elevated white blood cell count. Although vaso-occlusive crises result from microvessel occlusion, these findings at the macrovascular level suggest that SCD patients may also be vulnerable to mesenteric ischemic injury, especially in the setting of anemic heart failure from hemolysis.     

3‐Hydroxyisobutyryl‐CoA hydrolase deficiency in an infant with developmental delay and high anion gap acidosis

Due to the rarity of this disorder, paying attention to diagnostic clues is important. Low valine formula seems to be effective in improvement of patient''s symptoms. Prevention of consanguineous marriage is the best way to prevent this disease.     

Value of DNA testing in the diagnosis of sickle‐cell anemia in childhood in an environment with a high prevalence of other causes of anemia

BackgroundSickle‐cell anemia (SCA) is the most common genetic disease worldwide caused by a single mutation in the gene HBB. DNA testing can help to clarify the diagnosis when Hb electrophoresis is inconclusive. We evaluated the usefulness and feasibility of DNA‐based diagnosis of SCA in rural Central Africa.MethodsThis is a cross‐sectional study conducted from November 2016 to end October 2017 in the Hôpital Saint Luc de Kisantu, located 120 km from Kinshasa. This hospital offers the management of SCA patients, mainly identified using the Sickling test (Emmel test) combined with clinical features. We included patients aged 6 months to 18 years locally diagnosed as SCA, and we collected clinical and hematological data. All patients were offered Hb electrophoresis and DNA testing at the Center for Human Genetics of the University of Kinshasa.ResultsThis study included 160 patients. Hemoglobin capillary electrophoresis suggested that 136 (85%) were homozygote SS, 13 (8.1%) were heterozygote (AS), and 11 (6.9%) were homozygote normal (AA). DNA testing confirmed these electrophoresis findings, with the exception of four patients, two AS in electrophoresis were found SS due to recent transfusion, and two SS in electrophoresis were found AS because they have compound heterozygous form S/β°‐thalassemia. The diagnosis of SCA was therefore wrongly ascertained with Emmel test in 15% of patients.ConclusionThis study reveals a high proportion of false‐positive SCA diagnoses in a rural environment in Central Africa. This underlines the importance of DNA testing in conjunction with Hb electrophoresis.     

Longitudinal change of serum inter‐alpha‐trypsin inhibitor heavy chain H4, and its correlation with inflammation,multiorgan injury,and death risk in sepsis

BackgroundInter‐alpha‐trypsin inhibitor heavy chain H4 (ITIH4) inhibits infection‐induced inflammation and multiorgan injury through several methods. The present study aimed to estimate the association of serum ITIH4 with inflammatory cytokines, multiorgan injury, and death risk in sepsis patients.MethodsSerum samples were collected to detect ITIH4 by enzyme‐linked immunosorbent assay in 127 sepsis patients at admission (baseline), day (D)1, D3, and D7 after admission, as well as in 30 healthy controls (HCs). Additionally, 28‐day mortality was recorded in sepsis patients.ResultsITIH4 was reduced in sepsis patients versus HCs (median [interquartile range]: 147.9 [78.2–208.8] vs. 318.8 [237.2–511.4] ng/ml) (p < 0.001). In sepsis patients, ITIH4 was associated with the absence of cardiovascular and cerebrovascular disease history (p = 0.021). Additionally, ITIH4 was negatively correlated with tumor necrosis factor‐α (p < 0.001), interleukin (IL)‐1β (p < 0.001), IL‐6 (p = 0.019), IL‐17A (p = 0.002), and C‐reactive protein (p = 0.001), but positively related to IL‐10 (p = 0.007). Moreover, ITIH4 was also inversely associated with Acute Physiology and Chronic Health Evaluation II score (p = 0.002), Sequential Organ Failure Assessment (SOFA) score (p < 0.001), SOFA‐respiratory system score (p = 0.023), and SOFA‐renal system score (p = 0.007). Interestingly, ITIH4 gradually increased from baseline to D7 (p < 0.001); besides, ITIH4 at baseline (p = 0.009), D1 (p = 0.002), D3 (p < 0.001), and D7 (p = 0.015) were all decreased in sepsis deaths versus sepsis survivors.ConclusionSerum ITIH4 is raised from baseline to D7 after disease onset, and it reflects the reduction of systemic inflammation, disease severity, and 28‐day mortality for sepsis. However, further verification is required.     

Expression and prognostic significance of m6A‐related genes in TP53‐mutant non‐small‐cell lung cancer

BackgroundTP53 is an important tumor suppressor gene on human 17th chromosome with its mutations more than 60% in tumor cells. Lung cancer is the highest incidence malignancy in men around the world. N‐6 methylase (m6A) is an enzyme that plays an important role in mRNA splicing, translation, and stabilization. However, its role in TP53‐mutant non‐small‐cell lung cancer (NSCLC) remains unknown.MethodFirst, we investigated 17 common m6A regulators'' prognostic values in NSCLC. Then, after the establishment of risk signature, we explored the diagnostic value of m6A in TP53‐mutant NSCLC. Finally, gene set enrichment analysis (GSEA), gene ontology (GO) enrichment analysis, and differential expression analysis were used to reveal the possible mechanism of m6A regulators affecting TP53‐mutant NSCLC patients.ResultsStudy showed that nine m6A regulators (YTHDC2, METTL14, FTO, METTL16, YTHDF1, HNRNPA2B1, RBM15, KIAA1429, and WTAP) were expressed differently between TP53‐mutant and wild‐type NSCLC (p < 0.05); and ALKBH5 and HNRNPA2B1 were associated with the prognostic of TP53‐mutant patients. After construction of the risk signature combined ALKBH5 and HNRNPA2B1, we divided patients with TP53 mutations into high‐ and low‐risk groups, and there was a significant survival difference between two groups. Finally, 338 differentially expression genes (DEGs) were found between high‐ and low‐risk groups. GO enrichment analysis, PPI network, and GSEA enrichment analysis showed that m6A may affect the immune environment in extracellular and change the stability of mRNA.ConclusionIn conclusion, m6A regulators can be used as prognostic predictors in TP53‐mutant patients.     

Downregulation of Talin‐1 is associated with the increased expression of miR‐182‐5p and miR‐9‐5p in coronary artery disease

BackgroundEvidence indicates that the dysregulation of extracellular matrix (ECM) components can lead to cardiovascular diseases. The Talin‐1 (TLN1) gene is a major component of the ECM, and it mediates integrin adhesion to the ECM. In this study, we aimed to determine microRNAs (miRs) that regulate the expression of TLN1 and determine expression alterations in TLN1 and its targeting miRs in coronary artery disease (CAD).MethodsData sets of CAD and normal samples of blood exosomes were downloaded, and TLN1 was chosen as one of the genes with differential expressions in an in silico analysis. Next, miR‐182‐5p and miR‐9‐5p, which have a binding site on 3´‐UTR of TLN1, were selected using bioinformatics tools. Then, the miR target site was cloned in the psiCHECK‐2 vector, and direct interaction between the miR target site and the TLN1 3′‐UTR putative target site was investigated by luciferase assay. The expression of miR‐182‐5p, miR‐9‐5p, and TLN1 in the serum samples of CAD and non‐CAD individuals was assessed via a real‐time quantitative polymerase chain reaction.ResultsOur data revealed that miR‐182‐5p directly regulated the expression of TLN1. Moreover, miR‐182‐5p and miR‐9‐5p were significantly upregulated in the CAD group. Hence, both bioinformatics and experimental analyses determined the downregulated expression of TLN1 in the CAD samples.ConclusionsOur findings demonstrated that miR‐182‐5p and miR‐9‐5p could play significant roles in TLN1 regulation and participate in CAD development by targeting TLN1. These findings introduce novel biomarkers with a potential role in CAD pathogenesis.     

CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3

BackgroundLung cancer is the most commonly diagnosed cancer and leading cause of cancer death, with 80%–85% of non‐small cell lung cancer (NSCLC). Circular RNAs (circRNAs) have been shown to be promising early diagnostic and therapeutic molecular biomarkers for NSCLC. However, biological role and regulatory mechanism of circRNA WHSC1 (circWHSC1) in NSCLC are unknown. Therefore, we aim to explore the function and mechanism of circWHSC1 in NSCLC oncogenesis and progression.MethodsqRT‐PCR was used for circWHSC1 level evaluation; Kaplan‐Meier was used for survival analysis; bioinformatics, dual‐luciferase activity, and RNA pull‐down were used for evaluating competing endogenous RNA (ceRNA) network; cell viability, colony formation, apoptosis, migration, and invasion were used for cell function analysis; function gain and loss with rescue experiments were used for exploring mechanism of circWHSC1 in NSCLC development.ResultsSignificantly up‐regulated circWHSC1 and down‐regulated microRNA‐296‐3p (miR‐296‐3p) were identified in NSCLC tissues and cells. Up‐regulated circWHSC1 was associated with poor prognosis in NSCLC patients. MiR‐296‐3p was sponged by circWHSC1, and AKT serine/threonine kinase 3 (AKT3) was target of miR‐296‐3p; meanwhile, miR‐296‐3p over‐expression significantly down‐regulated AKT3 expression, and co‐transfecting anti‐miR‐296‐3p rescued circWHSC1 silence caused AKT3 down‐regulation. CircWHSC1 silence significantly inhibited colony formation, viability, invasion, and migration, while increased NSCLC cell apoptosis, which were partially rescued by anti‐miR‐296‐3p.ConclusionCircWHSC1 is an independent indicator of poor prognosis in NSCLC patients, and functions as a ceRNA of miR‐296‐3p to up‐regulate AKT3, consequently promotes NSCLC cell growth and metastasis. Targeting circWHSC1 might be a prospective strategy for diagnosis, therapeutics, and prognosis of NSCLC.     

The characteristics of upper airway edema in hereditary and acquired angioedema with C1‐inhibitor deficiency

BackgroundAngioedemas localized in the upper airway are potentially life threatening, and without proper treatment, they may lead to death by suffocation. Upper airway edemas (UAE) in bradykinin‐mediated angioedemas can even be the first symptoms of the disease.MethodsOur survey was performed with a retrospective long‐term follow‐up method from the medical history of 197 hereditary (C1‐INH‐HAE) and 20 acquired C1‐inhibitor deficiency (C1‐INH‐AAE), 3 factor XII and 3 plasminogen gene mutation (FXII‐HAE, PLG‐HAE) patients treated at our center between 1990 and 2020. The UAE group included edemas localized to the mesopharynx, hypopharynx, and larynx, as narrowing of these anatomical regions can lead to suffocation.Results98/197 C1‐INH‐HAE (47 families) and 13/20 C1‐INH‐AAE, 1/3 PLG‐HAE, 1/3 FXII‐HAE patients had experienced UAE at least once according to their medical history. In case of C1‐INH‐HAE patients, in 6/47 families who had undiagnosed ancestors had 13 members who died of suffocation. After the diagnosis, 1‐1 member of two families died of UAE. 44/64 C1‐INH‐HAE patients did not smoke, 20/64 did. The occurrence of UAE was significantly higher in smoker patients. We analyzed 7607 HAE attacks of 56/98 patients. Out of all attacks, the incidence of UAE in the C1‐INH‐HAE group was 4%, and 9.5% in the C1‐INH‐AAE group, respectively.ConclusionEarly diagnosis is key in bradykinin‐mediated angioedemas cases, since the patient must be provided with adequate treatment; and also it is essential to inform patients about the importance of avoiding the trigger factors and the early symptoms of UAE, as these measures could significantly decrease the incidence of lethal UAEs.